The aim of the present study was to clarify the relationship between topoisomerase-I (topo-I) activity and sensitivity to second-line chemotherapy consisting of cisplatin and camptothecin-11 (CPT-11) in patients with ovarian cancer. Thirty Japanese women with relapsed epithelial ovarian cancer who received treatment at Tottori University Hospital or Kurume University Hospital between 1992 and 1997 were included in this study. All patients had initially undergone chemotherapy consisting of cisplatin, doxorubicin and cyclophosphamide (CAP). All subjects exhibited measurable lesions and received second-line chemotherapy consisting of 50 to 60 mg/m(2) CPT-11 on days 1, 8 and 15 and 60 mg/m(2) cisplatin on day 1. Tumor samples were obtained in the period between initial and second-line chemotherapy. Topo-I activity was assayed by relaxation of supercoiled plasmid substrate DNA. Of the 30 patients, 18 responded to second-line chemotherapy and 12 did not. We found no significant difference in patient characteristics in responders and non-responders. The interval from the end of the initial course of chemotherapy to the beginning of the second-line chemotherapy did not significantly differ in the 2 groups. The minimum amount of extraction showing complete DNA relaxation in non-responders was significantly greater than that in responders (201.7 +/- 92.5 vs. 124.1 +/- 59.4 ng; p = 0.0164). In 8 cases whose samples could be obtained before and after CAP, the amount of protein significantly decreased after CAP therapy (286.4 +/- 142.1 vs. 138.5 +/- 97.8 ng; p = 0.0294). Topo-I activity, which is enhanced by CAP therapy, can play an important role in sensitivity to CPT-11.
Copyright 1999 Wiley-Liss, Inc.